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Uranium Toxicity
Clinical Assessment

Learning Objectives

Upon completion of this section, you will be able to

identify the primary focus of the exposure and medical history and

describe the most typical biomarkers of effect.

Introduction

In general, uranium at levels typically encountered in the community or in the workplace when normal protective measures are enforced has not been found to result in adverse health effects. Workers in the uranium milling industry have been shown to have early signs of renal toxicity, but these usually resolve after exposure is ended. Autopsies of highly exposed workers who died years after exposure ended found apparent complete repair of affected renal tissues.

Uranium exposures in industrial settings often occur in the presence of other known toxicants such as

silica dust,

diesel exhaust particles,

radon, and

radium.

Individuals who are exposed to uranium in an occupational setting may need to be assessed for these types of concurrent exposures. A typical patient evaluation should include

an exposure history,

a medical history,

a physical exam, and

an assessment of biomarkers of exposure and effect.

Exposure History

A detailed exposure history is an important step in evaluating a patient who may be at risk for health outcomes related to uranium exposure. In general, uranium at levels typically encountered in the community or in the workplace when normal protective measures are enforced has not been found to result in short-term or long-term adverse health effects. However, other concurrent exposures may be significant and could result in more serious health outcomes requiring further evaluation and treatment. Uranium exposure can result in reversible lung or kidney damage.

A work history, including past occupations in which the patient may have been exposed directly or indirectly, is relevant in evaluating their exposures. Additionally, exposure histories should be evaluated in communities where naturally occurring uranium is elevated in air and water or where milling operations occur. Contact the local or state health department for assistance with finding information on uranium levels in air and water, especially levels in local aquifers likely to be tapped by private wells.

Medical History

Knowing the complete medical history of a patient who has been exposed to uranium can help in making an accurate diagnosis. It is especially important to ask about renal function, since the kidney is the target organ for inhaled, ingested, and dermally absorbed uranium.

In the case study, the findings are very nonspecific because uranium has no specific biomarkers of effect. The health care provider may wish to consider the possibility of bronchial irritation or pulmonary fibrosis associated with respective current and past inhalation overexposure to uranium.

Physical Exam

The primary toxic effect of uranium exposure is nephrotoxicity. There are very few physical findings associated with renal disease unless it is very severe. However, it is important to check patients for hypertension and edema.

Biomarkers of Exposure and Effect

Finding a measurable amount of uranium in urine does not mean that the level of uranium causes an adverse health effect. According to the Third National Report on Human Exposure to Environmental Chemicals, urine uranium levels were measured in a subsample of the National Health and Nutrition Examination Survey (NHANES). Participants in this survey were aged 6 years and older during 1999-2002. Participants were selected within the specified age range to be a representative sample of the U.S. population.

The analytical method measured only levels of the U-238 isotope (99% naturally occurring) and not levels of the U-235 isotope (U-235 is higher in enriched uranium used as nuclear fuel). The 95th percentile of urinary uranium concentrations was .034 micrograms/gram (µg/g) creatinine in the 1999-2000 survey years and .040 µg/g creatinine in the 2001-2002 survey years for the U.S. population aged 6 years and older [CDC 2009].

These urinary uranium levels provide physicians with a reference range so that they can determine whether people have been exposed to higher levels of uranium than are found in the general population. Whether uranium at these levels is cause for health concern is unknown. More research is needed. Urinary uranium analyses are not routinely available at typical hospital laboratories.

A study looking at 105 people exposed to well water in South Carolina containing natural uranium in the range of 1.8 to 7770 µg/Liter (L) (median 157 µg/L) showed urinary levels of uranium as high as 9.55 µg/L (median 0.162 µg/L) [Orloff et al. 2004].

The best way to evaluate acute uranium exposure and possible effects is through urine tests for uranium concentration (exposure) and markers of renal effects. Indicators of renal toxicity include urinary catalase, proteinuria, aminoaciduria, and clearance of β2-microglobulin relative to creatinine.

The majority of uranium is cleared quickly from the body; therefore, high uranium concentrations in the urine (>100 µg/L) reflect current or recent exposures, while low concentrations (<40 µg/L) are most likely a result of past exposures or typical background exposure.

It is important to re-emphasize that elevated urine uranium concentrations indicate exposure, but they do not necessarily indicate adverse effects. In addition, biomarkers of effect (nephrotoxicity) are not unique to uranium exposure and should be considered in the whole of a patient's exposure and medical history.

No other laboratory tests are likely to be useful.

Differential Diagnosis

There are multiple causes of renal dysfunction; therefore, it is important to include a work history or an exposure history. If there is none, document the possibility of environmental exposure for communities with elevated levels of uranium in soil and water, as well as evaluate biomarkers of exposure and effect. In addition, there is no evidence for an effect of uranium as a carcinogen; other alpha-emitters are known to have greater effects and should be considered in evaluating cancer outcomes (e.g., radon exposure in uranium miners, especially in those who also smoke).

Key Points

The exposure history focuses on occupational exposure or community exposure where uranium is elevated in soil or water.

The medical history focuses on renal function.

The most typical finding is elevated β2-microglobulin, proteinuria, and glucosuria.

Health effects from uranium are not easily differentiated from other causes without a clear history of exposure.

Progress Check

11. The most typical biomarkers of effect for a patient with uranium nephrotoxicity is

A. The biomarkers of effect are not unique to uranium exposure.
B. Other concurrent exposures may be more toxic and more important to future patient care.
C. It is important to determine if exposures are ongoing or occurred in the past.
D. All of the above.